Sorbs1 and -2 Interact with CrkL and Are Required for Acetylcholine Receptor Cluster Formation

Mol Cell Biol. 2015 Nov 2;36(2):262-70. doi: 10.1128/MCB.00775-15. Print 2016 Jan 15.

Abstract

Crk and CrkL are noncatalytic adaptor proteins necessary for the formation of neuromuscular synapses which function downstream of muscle-specific kinase (MuSK), a receptor tyrosine kinase expressed in skeletal muscle, and the MuSK binding protein Dok-7. How Crk/CrkL regulate neuromuscular endplate formation is not known. To better understand the roles of Crk/CrkL, we identified CrkL binding proteins using mass spectrometry and have identified Sorbs1 and Sorbs2 as two functionally redundant proteins that associate with the initiating MuSK/Dok-7/Crk/CrkL complex, regulate acetylcholine receptor (AChR) clustering in vitro, and are localized at synapses in vivo.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Line
  • Mice
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Muscle Fibers, Skeletal / metabolism*
  • Mutation
  • Myoblasts / metabolism
  • Nuclear Proteins / metabolism*
  • Protein Interaction Maps
  • RNA Interference
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins
  • Receptors, Cholinergic / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • CRKL protein
  • Microfilament Proteins
  • Nuclear Proteins
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Receptors, Cholinergic
  • Sorbs2 protein, mouse
  • ponsin